Abstract
The very late antigens, VLA-4 and VLA-5 belong to the β1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+ CD4- CD8- γδTCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low γδT cells specifically adhere to FN. The binding capacity is inhibited by the synthetic peptide GRGDSP which inhibits adhesion mediated by VLA-5 and a functional mAb directed against the α4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting γδ T cells cultured on coimmobilized anti-TCRδ1 mAb and FN or the 40 kDa fragment (which contains the adhesion site in the IIICS domain recognized by VLA-4) for 96 h in the absence of exogeneous IL-2 showed significant increase in proliferation when compared to that of resting γδ T cells cultured on immobilized anti-TCRδ1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCRδ1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting γδ T cells induced by cross-linked TCRδ1. These results suggest that the γδ T cell β1 integrins, VLA-4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 101-108 |
| Number of pages | 8 |
| Journal | Immunology Letters |
| Volume | 35 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1993 |
| Externally published | Yes |
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Keywords
- Costimulation
- Human γδ TCR
- β1 Integrins
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Adhesion and costimulation of proliferative responses of human γδ T cells by interaction of VLA-4 and VLA-5 with fibronectin. / Avdalovic, Mark V; Fong, Dana; Formby, Bent.
In: Immunology Letters, Vol. 35, No. 2, 1993, p. 101-108.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adhesion and costimulation of proliferative responses of human γδ T cells by interaction of VLA-4 and VLA-5 with fibronectin
AU - Avdalovic, Mark V
AU - Fong, Dana
AU - Formby, Bent
PY - 1993
Y1 - 1993
N2 - The very late antigens, VLA-4 and VLA-5 belong to the β1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+ CD4- CD8- γδTCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low γδT cells specifically adhere to FN. The binding capacity is inhibited by the synthetic peptide GRGDSP which inhibits adhesion mediated by VLA-5 and a functional mAb directed against the α4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting γδ T cells cultured on coimmobilized anti-TCRδ1 mAb and FN or the 40 kDa fragment (which contains the adhesion site in the IIICS domain recognized by VLA-4) for 96 h in the absence of exogeneous IL-2 showed significant increase in proliferation when compared to that of resting γδ T cells cultured on immobilized anti-TCRδ1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCRδ1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting γδ T cells induced by cross-linked TCRδ1. These results suggest that the γδ T cell β1 integrins, VLA-4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules.
AB - The very late antigens, VLA-4 and VLA-5 belong to the β1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+ CD4- CD8- γδTCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low γδT cells specifically adhere to FN. The binding capacity is inhibited by the synthetic peptide GRGDSP which inhibits adhesion mediated by VLA-5 and a functional mAb directed against the α4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting γδ T cells cultured on coimmobilized anti-TCRδ1 mAb and FN or the 40 kDa fragment (which contains the adhesion site in the IIICS domain recognized by VLA-4) for 96 h in the absence of exogeneous IL-2 showed significant increase in proliferation when compared to that of resting γδ T cells cultured on immobilized anti-TCRδ1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCRδ1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting γδ T cells induced by cross-linked TCRδ1. These results suggest that the γδ T cell β1 integrins, VLA-4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules.
KW - Costimulation
KW - Human γδ TCR
KW - β1 Integrins
UR - http://www.scopus.com/inward/record.url?scp=0027477636&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027477636&partnerID=8YFLogxK
U2 - 10.1016/0165-2478(93)90077-F
DO - 10.1016/0165-2478(93)90077-F
M3 - Article
VL - 35
SP - 101
EP - 108
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 2
ER -